Corstiaan C. Breugem

Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infants

BACKGROUND Infantile hemangioma (IH) is a frequently encountered tumor with a potentially complicated course. Recently, propranolol was discovered to be an effective treatment option. OBJECTIVE To describe the effects and side effects of propranolol treatment in 28 children with (complicated) IH. METHODS A protocol for treatment of IH with propranolol was designed and implemented. Propranolol was administered to 28 children (21 girls and 7 boys, mean age at onset of treatment: 8.8 months). RESULTS All 28 patients had a good response. In two patients, systemic corticosteroid therapy was tapered successfully after propranolol was initiated. Propranolol was also an effective treatment for hemangiomas in 4 patients older than 1 year of age. Side effects that needed intervention and/or close monitoring were not dose dependent and included symptomatic hypoglycemia (n = 2; 1 patient also taking prednisone), hypotension (n = 16, of which 1 is symptomatic), and bronchial hyperreactivity (n = 3). Restless sleep (n = 8), constipation (n = 3) and cold extremities (n = 3) were observed. LIMITATIONS Clinical studies are necessary to evaluate the incidence of side effects of propranolol treatment of IH. CONCLUSIONS Propranolol appears to be an effective treatment option for IH even in the nonproliferative phase and after the first year of life. Potentially harmful adverse effects include hypoglycemia, bronchospasm, and hypotension.

Complications of otoplasty: a literature review

Over 200 otoplasty techniques have been described in the current literature. However, relatively few articles focus on the associated complication rates. The goal of this review is to examine the incidence of complication rates associated with otoplasty procedures. An electronic search of the Pubmed database yielded 205 articles with significant overlap in search results. Twenty articles published between 2000 and 2007 adhered to our inclusion criteria. Early complications included in this review were haematoma, bleeding, infection, skin necrosis and wound dehiscence; late complications included suture extrusion, scarring, hypersensitivity, asymmetry and inaesthetic results. The cumulative incidence of early complications was low and varied from 0% to 8.4%, with the exception of two outliers. Although cumulative late complication incidences varied greatly from 0% to 47.3%, complication rates on the higher end of the spectrum were not accompanied with revision rates of the same magnitude. Comparison of the different articles was made difficult by the lack of a uniform calculation method for complication incidence, variable follow-up length and data collection, inconsistent use of operation technique and publication bias. Recommendations for future studies include: consistent use of operative technique or at least differentiate between the used surgical techniques when presenting complication rates, inclusion of only patients with bilateral primary procedures, considering each operated ear as an independent variable when calculating complication incidence and a minimum follow-up period of 2 years, with both objective and subjective data collection.

Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2

The alveolar cleft in patients with clefts of lip, alveolus and palate (CLAP) is usually reconstructed with an autologous bone graft. Harvesting of autologous bone grafts is associated with more or less donor site morbidity. Donor site morbidity could be eliminated if bone is fabricated by growth factor-aided tissue engineering. The objective of this review was to provide an oversight on the current state of the art in growth factor-aided tissue engineering with regard to reconstruction of the alveolar cleft in CLAP. Medline, Embase and Central databases were searched for articles on bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 7, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor and platelet-rich plasma for the reconstruction of the alveolar cleft in CLAP. Two-hundred ninety-one unique search results were found. Three articles met our selection criteria. These three selected articles compared BMP-2-aided bone tissue engineering with iliac crest bone grafting by clinical and radiographic examinations. Bone quantity appeared comparable between the two methods in patients treated during the stage of mixed dentition, whereas bone quantity appeared superior in the BMP-2 group in skeletally mature patients. Favourable results with BMP-2-aided bone tissue engineering have been reported for the reconstruction of the alveolar cleft in CLAP. More studies are necessary to assess the quality of bone. Advantages are shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost.

Auricular reconstruction using biofabrication-based tissue engineering strategies

Auricular malformations, which impose a significant social and psychological burden, are currently treated using ear prostheses, synthetic implants or autologous implants derived from rib cartilage. Advances in the field of regenerative medicine and biofabrication provide the possibility to engineer functional cartilage with intricate architectures and complex shapes using patient-derived or donor cells. However, the development of a successful auricular cartilage implant still faces a number of challenges. These challenges include the generation of a functional biochemical matrix, the fabrication of a customized anatomical shape, and maintenance of that shape. Biofabrication technologies may have the potential to overcome these challenges due to their ability to reproducibly deposit multiple materials in complex geometries in a highly controllable manner. This topical review summarizes this potential of biofabrication technologies for the generation of implants for auricular reconstruction. In particular, it aims to discuss how biofabrication technologies, although still in pre-clinical phase, could overcome the challenges of generating and maintaining the desired auricular shapes. Finally, remaining bottlenecks and future directions are discussed.

Robin Sequence: Clearing Nosologic Confusion

OBJECTIVE To gather evidence surrounding the confusion in the classification of Robin sequence and inform those who have the power to make the changes in defining this symptom complex. METHOD A questionnaire was sent to all participating cleft palate teams (N=204) of the American Cleft Palate-Craniofacial Association. The questionnaire identified the precise, different characteristics for diagnosing Robin sequence and evaluated whether the difference between a retrognathia and micrognathia influenced the diagnosis process. We subsequently also investigated whether the cleft type (i.e., U-shaped versus V-shaped) had any influence in the decision-making process. A PubMed literature review of the 50 most recent manuscripts about Robin sequence was evaluated also. RESULTS Seventy-three questionnaires were received. This 35% response rate revealed 14 different definitions of Robin sequence. A PubMed literature review of 50 consecutive manuscripts revealed 15 different descriptions. CONCLUSION This study confirms that nosologic confusion is widespread with regard to defining Robin sequence. This has implications for evaluating Robin sequence, giving advice about the prognosis and genetic counseling, and refining treatment options.

Use of magnetic resonance imaging for the evaluation of vascular malformations of the lower extremity

Vascular malformations are anatomically subdivided according to the predominant channel anomaly into either capillary, arterial, venous, lymphatic, or combinations. They can be further subdivided into high‐ or low‐flow malformations. Any lesion that has an arterial component is considered a high‐flow malformation. Once the diagnosis of a vascular malformation is made, it is of paramount importance to define not only the flow characteristics but also the full range of extension, because the prognosis and appropriate treatment vary substantially for each type of anomaly. The two most useful noninvasive imaging techniques for assessing vascular malformations are magnetic resonance imaging (MRI) and ultrasonography. The aim of this review is to give surgeons involved in treating patients with vascular malformations an opportunity to gain some background on MRI scans when assessing vascular malformations. Although MRI is a powerful modality for assessing vascular malformations, we will also discuss some of the limitations of MRI. We further suggest a diagnostic flow chart developed on the basis of MRI features designed to help determine the composition of a vascular birthmark when intervention is anticipated. (Plast. Reconstr. Surg. 108: 870, 2001.)

Outcome of velopharyngoplasty in patients with velocardiofacial syndrome.

OBJECTIVE To compare the outcomes of surgical correction of velopharyngeal insufficiency (VPI) in patients with velocardiofacial syndrome (VCFS) and a non-VCFS group. DESIGN Twenty-five patients with VCFS (16 girls and 9 boys) underwent palatal lengthening for VPI between 1986 and 2001. The mean age at surgery was 6.4 years. Revision was defined as the need for secondary sphincter pharyngoplasty as determined by speech investigation, nasal endoscopy, and acoustic nasometry. A comparison was made to a control group made up of a randomized group of patients without VCFS who underwent palatal lengthening for VPI (32 patients: 10 girls and 22 boys). SETTING Wilhelmina Childrens Hospital, a tertiary referral center in Utrecht, the Netheralands. PATIENTS A total of 57 patients who underwent palatal lengthening for VPI, 25 with VCFS and 32 without VCFS. INTERVENTIONS Primary surgery consisted of a palatal lengthening technique. If revision was needed, a sphincter pharyngoplasty was carried out. MAIN OUTCOME MEASURES Pharyngeal function was assessed using perceptual speech investigation, nasal endoscopy, and acoustic nasometry. RESULTS In the VCFS group, 16% of the patients required surgical revision (4 of 25). These patients were slightly older at the time of primary surgery than those who did not require surgical revision (mean age, 6 vs 5.5 years). In the control group, no patients required revision. Preoperative speech analysis showed a more pronounced VPI in the VCFS group than in the control group. Outcomes of endoscopy and speech hypernasality improved significantly more in the control group than in the VCFS group. Improvement in the results of acoustic nasometry did not differ significantly between the 2 groups. CONCLUSIONS Treatment of VPI using palatal lengthening in children with VCFS is both safe and effective. The discrepancy in improvement between the speech analysis and the nasal endoscopy results within the VCFS group indicates that mechanical improvement does not necessarily correspond to an improvement in speech and emphasizes the complexity of speech disorders found in VCFS.

Phenotypic variability in a family with capillary malformations caused by a mutation in the RASA1 gene

Hereditary capillary malformations are known to be caused by mutations in the RASA1 gene. The associated phenotype is still subject of debate. The purpose of this study was to conduct a RASA1 mutation analysis in the family that led to the initial discovery of the 5q locus, and to delineate the associated phenotype. A novel truncating mutation was identified in all clinically affected individuals and in none of the unaffected members. The associated phenotype was widely variable; all individuals had multifocal CM with at least one area of high flow. Various additional features were observed, some previously reported and others novel, including limb overgrowth, varicosities, possible lymphatic malformations, localized hyperhidrosis and exercise induced redness. The cause of this wide intramutational phenotypic variability remains to be elucidated.

Magnetic resonance imaging findings of vascular malformations of the lower extremity

Vascular malformations are congenital lesions resulting from a defect during embryogenesis. Magnetic resonance imaging (MRI) is a very effective method for demonstrating detailed information regarding involved structures, extent, and flow characteristics of vascular malformations. In previous MRI studies, most of the emphasis is laid on the difference between high‐ and low‐flow lesions, whereas little detailed information is available about the extent of local tissue involvement. These additional characteristics may influence the approach in treating these malformations and improve understanding of the pathogenesis. We retrospectively reviewed MRI scans of 40 patients with vascular malformations of the lower extremity. Thirty‐four patients had low‐flow lesions, and six had high‐flow lesions. Of the low‐flow lesions, 23 patients (67.6 percent) had muscle infiltration, with four of the six highflow lesions having muscle infiltration. Nine of the 11 male patients (81.8 percent) with low‐flow lesions had associated muscle infiltration, in comparison with 14 of the 23 female patients (60.9 percent) with low‐flow lesions (p = 0.206). Eighty percent of the vascular malformations located on the thigh with muscle involvement had involvement of the anterior muscle group, whereas 86.6 percent of the patients with a vascular malformation located on the leg and with associated muscle involvement had at least the posterior muscle group involved (p = 0.0049). Ten patients (25 percent) of the whole group had bone infiltration. Low‐flow lesions often had multifocal lesions (20.6 percent), whereas associated muscle atrophy was visible in 10 low‐flow lesions and in two high‐flow lesions. In low‐flow lesions with muscle infiltration (n = 23), 43 percent (n = 10) had associated surrounding muscle atrophy (p = 0.009). Hypertrophy of the subcutaneous tissue was visible in 11 low‐flow patients (32.4 percent). The high amount of muscle and bone involvement in vascular malformations of the lower extremity is emphasized with this study. Of particular interest was the difference in affected muscle groups. The angiosome concept is used to explain this preponderance, and we feel the angiosome concept could also be used when assessing possible intervention. The surrounding muscle atrophy and multifocal nature of these anomalies are further important considerations when assessing the possibility of intervention. (Plast. Reconstr. Surg. 108: 878, 2001.)

Is cardiovascular evaluation necessary prior to and during beta-blocker therapy for infantile hemangiomas?: A cohort study.

BACKGROUND Although consensus guidelines for pretreatment evaluation and monitoring of propranolol therapy in patients with infantile hemangiomas (IH) have been formulated, little is known about the cardiovascular side effects. OBJECTIVES We sought to analyze cardiovascular evaluations in patients with IH at baseline and during treatment with an oral beta-blocker. METHODS Data from 109 patients with IH were retrospectively analyzed. Patient and family history, pretreatment electrocardiogram (ECG), heart rate, and blood pressure were evaluated before initiation of beta-blocker therapy. Blood pressure and standardized questionnaires addressing side effects were evaluated during treatment. RESULTS Questionnaire analyses (n = 83) identified 3 cases with a family history of cardiovascular disease in first-degree relatives. ECG findings were normal in each case and no serious complication of therapy occurred. ECG abnormalities were found in 6.5% of patients but there were no contraindications to beta-blocker therapy and no major complications. Hypotension in 9 patients did not require therapy adjustment. In all, 88 parents (81%) reported side effects during beta-blocker treatment. LIMITATIONS The relatively small patient cohort is a limitation. CONCLUSION Pretreatment ECG is of limited value for patients with an unremarkable cardiovascular history and a normal heart rate and blood pressure. Hypotension may occur during treatment.